DESCRIPTION Exposure to bone-seeking radionuclides such as Pu, Am and Ra presents a substantial health risk and is of considerable public concern. The present models used to establish "safe" limits and to protect humans from the harmful effects of internally-deposited alpha emitting nuclides are based on incomplete data and in some cases clearly erroneous assumptions. Some of the deficiencies in the current model include incorrect assumptions for the partitioning of nuclides between trabecular and cortical bone, incorporation and retention of Pu on bone surfaces, the nature of the cellular composition of the endosteum, and contribution of marrow deposits. Using a unique and extensive collection of specimens, that the aplicants have in their possession from previous beagle dog studies, the deficiencies in the present model will be addressed with the following aims. 1) Static and dynamic physical data from bone sites and associated dosimetric parameters will be determined. 2) From neutron-induced autoradiographs (NIAR), the tissue parameters important for a local dose model will be determined, including osseous tissue and marrow contents. 3) Using fluorochrome- based histomorphometric methods, the remodelling and turnover characteristics of different bone sites will be correlated with Pu concentrations at these same sites. 4) Areal bone cell densities will be quantified and radiation doses and hit frequencies to specific cell populations will be determined. The local dose model will be correlated with known probabilities of tumor occurrence at specific sites and then extrapolated to humans. Pu-exposed human bone will be obtained and static and local dosimetric data obtained. This will provide a stronger basis for comparing the animal data with human. This study will provide a considerably more accurate biokinetic dose/effect model, based on experimental data supplemented with human observations, for predicting the consequences of human exposure to bone-seeking radionuclides. These studies will also provide fundamental new knowledge about the biokinetics of metals in skeletal tissues.